Method for producing orotic acid derivative

Abstract

Provided is a method for producing an orotic acid derivative, the method comprising a condensation step of performing, under a basic condition, a condensation reaction between an orotic acid halide represented by General Formula (I) and a compound represented by General Formula (II) to generate an orotic acid derivative represented by General Formula (III); and a neutralization crystallization step of precipitating crystals of orotic acid by neutralization crystallization to separate a liquid containing the orotic acid derivative from the crystals of orotic acid, after the condensation step. In General Formula (I), (II), or (III), X is a halogen atom, and A is a group represented by General Formula (A-1) or (A-2). In General Formula (A-1) or (A-2), R1 is a hydrogen atom or an organic group, and R2 and R3 are each independently an organic group. In a case where R1 is an organic group, R1 and R2 may be bonded to each other to form a ring.

What is claimed is: 
     
       1. A method for producing an orotic acid derivative, comprising:
 performing, under a basic condition, a condensation reaction between an orotic acid halide represented by General Formula (I) and a compound represented by General Formula (II) to generate an orotic acid derivative represented by General Formula (III); and 
 precipitating crystals of orotic acid by neutralization crystallization to separate a liquid containing the orotic acid derivative from the crystals of orotic acid, after the condensation reaction, 
 
       
         
           
           
               
               
           
         
         wherein X is a halogen atom, and A is a group represented by General Formula (A-1) or (A-2); 
       
       
         
           
           
               
               
           
         
         wherein R 1  is a hydrogen atom or an organic group, and R 2  and R 3  are each independently an organic group, in a case where R 1  is an organic group, R 1  and R 2  may be bonded to each other to form a ring, and * is a bonding position at which the hydrogen atom in General Formula (II) is bonded. 
       
     
     
       2. The method for producing an orotic acid derivative according to  claim 1 , wherein in General Formula (A-1), le is a hydrogen atom or an organic group having 1 to 10 carbon atoms, and R 2  is an organic group having a carboxy group and having 1 to 15 carbon atoms, and
 in General Formula (A-2), R 3  is an organic group having 1 to 15 carbon atoms. 
 
     
     
       3. The method for producing an orotic acid derivative according to  claim 1 , wherein the compound represented by General Formula (II) is an amino acid. 
     
     
       4. The method for producing an orotic acid derivative according to  claim 3 , wherein the amino acid is glutamic acid. 
     
     
       5. The method for producing an orotic acid derivative according to  claim 1 , to wherein a solvent used in the condensation reaction is a non-halogenic solvent. 
     
     
       6. The method for producing an orotic acid derivative according to  claim 5 , wherein the solvent is a water-containing solvent. 
     
     
       7. The method for producing an orotic acid derivative according to  claim 6 , wherein the solvent is a two-phase solvent of an organic solvent and water. 
     
     
       8. The method for producing an orotic acid derivative according to  claim 7 , wherein the organic solvent is tetrahydrofuran or toluene. 
     
     
       9. The method for producing an orotic acid derivative according to  claim 1 , wherein a pH of a liquid phase is set to 4 to 6 in the neutralization crystallization step. 
     
     
       10. The method for producing an orotic acid derivative according to  claim 1 , further comprising subjecting the liquid containing the orotic acid derivative to secondary neutralization crystallization to precipitate crystals of the orotic acid derivative, after the neutralization crystallization. 
     
     
       11. The method for producing an orotic acid derivative according to  claim 10 , wherein a pH of a liquid phase is set to 0.5 to 2 in the secondary neutralization crystallization. 
     
     
       12. The method for producing an orotic acid derivative according to  claim 10 , further comprising collecting the crystals of the orotic acid derivative, after the secondary neutralization crystallization. 
     
     
       13. The method for producing an orotic acid derivative according to  claim 1 , further comprising reacting an orotic acid with a thionyl halide to generate the orotic acid halide, before the condensation reaction. 
     
     
       14. The method for producing an orotic acid derivative according to  claim 1 , wherein the orotic acid halide is orotic acid chloride.